The cellular and biochemical bases of inherited complement disorders will be studied using strains of mice with inherited C5 deficiency as the experimental model. These studies have valuable application to the understanding of the molecular basis of human C5 deficiency and will broaden concepts related to human complement deficiencies and to the biosynthesis of human complement proteins. Parallel studies will be done exploring biosynthetic mechanisms by normal resident mouse peritoneal macrophages for comparison; altered regulation by the inflammatory macrophage will also be investigated. The investigation will be conducted as follows: 1. Characterization of the mechanism of C5 biosynthesis by mouse peritoneal macrophages by kinetic and biochemical analysis, with an examination of the role of glycosylation and the steps in the conversion of pro-C5 to C5. 2. Determination of the biochemical basis of C5 deficiency in different strains of C5 deficient mice. 3. The molecular genetics of polymorphic pro-C5 variants will be studied. This is an extension of preliminary observations identifying two electrophoretics pro-C5 variants secreted by mouse peritoneal macrophages in culture. 4. The cellular and biochemical basis of C5 biosynthesis in relation to the pathophysiology of the macrophage will be examined and a comparison made with C5 deficient mouse. These studies will lead to increased understanding of the inherited and noninherited disorders of C5 in the human.